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Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>A new user comparator study design was conducted in patients \u226550 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer\u2019s disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 96\u2009140 and 16\u2009451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4\u00b18.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70\u20130.94), 0.79 (0.63\u20131.00) and 0.91 (0.79\u20131.04). Stronger associations were observed in patients who were younger (&lt;75 years old), Caucasian, and with moderate renal function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjdrc-2022-003036","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:25:13Z","timestamp":1663223113000},"page":"e003036","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Comparative effect of metformin versus sulfonylureas with dementia and Parkinson\u2019s disease risk in US patients over 50 with type 2 diabetes mellitus"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-1478","authenticated-orcid":false,"given":"Danielle","family":"Newby","sequence":"first","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"},{"name":"Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Brent","family":"Linden","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmina","family":"Molero","sequence":"additional","affiliation":[{"name":"Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institute, Stockholm, Sweden"},{"name":"Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Winchester","sequence":"additional","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Sproviero","sequence":"additional","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Upamanyu","family":"Ghose","sequence":"additional","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqin S","family":"Li","sequence":"additional","affiliation":[{"name":"Neuroscience, Janssen Research and Development, Titusville, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenore J","family":"Launer","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia M van","family":"Duijn","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, University of Oxford, Oxford, UK"},{"name":"Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejo J","family":"Nevado-Holgado","sequence":"additional","affiliation":[{"name":"Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"2025073113183414000_10.5.e003036.1","unstructured":"Martin Prince A , Wimo A , Guerchet M . 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